UPMC Physician Resources

Pediatric Neurology Researcher Receives NIH Grant

PITTSBURGH, Feb. 3, 2015 – Sharyl L. Fyffe-Maricich, PhD, assistant professor of pediatrics at the University of Pittsburgh School of Medicine, has been awarded an NIH Research Project Grant (R01) for her submission, “The Role of ERK1/2 MAP Kinase Signaling in CNS Myelination.” The grant was awarded on Dr. Fyffe-Maricich’s first submission, which is a high honor. Her immediate goal is to improve therapy for multiple sclerosis (MS) and other demyelinating diseases.

A member of the Society for Neuroscience, Dr. Fyffe-Maricich joined the Division of Child Neurology at Children’s Hospital of Pittsburgh of UPMC in 2013 and quickly established a highly productive lab. She was the focus of a recent documentary produced by the National Multiple Sclerosis Society about her research.

To see Dr. Fyffe-Maricich in the documentary, please visit the National Multiple Sclerosis Society’s YouTube page.

Personalized Medicine to Reduce Adverse Drug Outcomes in People with Mental Illness

PITTSBURGH, Feb. 3, 2015 – Geneticists at the University of Pittsburgh Graduate School of Public Health will provide their scientific expertise to a new initiative aimed at preventing and reducing the adverse effects of medications in people with mental illnesses.

The research project will take a personalized medicine approach to managing drug therapy by analyzing each patient’s genetic makeup to determine potential adverse reactions to medications. Funded by the Polk Foundation, it will be led by NHS Human Services, one of the nation’s largest providers of human services, in collaboration with Pitt Public Health; CareKinesis Inc., a medication therapy management services provider; and Coriell Life Sciences, a pharmacogenomics testing vendor.

“An individual’s genetic makeup defines how many common drugs are processed by the body and who is at risk for an adverse drug response from such therapies,” said Dietrich Stephan, Ph.D., professor and chair of the Department of Human Genetics at Pitt Public Health. “Individuals can suffer immensely from the very drugs that are meant to improve their health if given drugs they cannot tolerate, often resulting in increased emergency room visits and elevated health care costs.”

For example, some people are genetically predisposed to metabolize certain drugs faster than the average person, causing them to have a stronger, more immediate response to medication. When someone is prescribed multiple medications, such responses can cause unexpected and potentially dangerous drug interactions.

“The people at highest risk, such as the aged and mentally ill, often are prescribed a multitude of drugs with no insight into their genetic susceptibilities,” said Dr. Stephan, who also serves as associate director of the Institute for Personalized Medicine, a collaboration between Pitt and UPMC. “In this study, we aim to systematically implement comprehensive genetic testing in these populations and develop the evidence around improved outcomes and reduced costs that allows such testing to be broadly delivered to the general population and reimbursed by insurers. The Institute for Personalized Medicine, as part of UPMC, has the scale to be able to broadly implement pharmacogenomics to improve lives across a multitude of providers both nationally and internationally.”

Dr. Stephan serves as chair of the clinical advisory panel for the 28-month, $350,000 initiative, which is funded by a grant from the Polk Foundation to NHS Human Services Foundation, the charitable arm of NHS Human Services.

“Our primary goal is to increase the quality of life for individuals in behavioral health services, and the funding received to conduct this important research is a significant step in the right direction,” said Joe Martz, chief executive officer of NHS Human Services.

Study participants will be selected from a pool of adults with mental illnesses served by NHS in Allegheny, Beaver, Dauphin and Lehigh counties, and who currently are prescribed or will be prescribed at least one psychotropic medication during the study period. Participation in the study will be voluntary and oversight will be provided by Robin Grubs, Ph.D., director of Pitt’s genetic counseling program, one of the country’s oldest and most rigorous counseling programs, and also by nationally recognized ethicist Lisa Parker, Ph.D., of Pitt’s Center for Bioethics & Health Law, who also provides oversight for the National Human Genome Research Institute.

New Center at Children’s Hospital of Pittsburgh of UPMC Offers Hope to Kids From Around the World With Rare Diseases

PITTSBURGH, Feb. 2, 2015Children’s Hospital of Pittsburgh of UPMC has established a Center for Rare Disease Therapy, focused on providing new, sometimes breakthrough treatments for infants, children, adolescents and young adults from around the world who have been diagnosed with rare diseases and disorders. The center brings together experts from across the hospital and health system to tackle complex problems.

“Patient families travel from all over the world to Children’s Hospital looking for hope and answers, especially when they can’t find it at their local hospital. We are different in that we have developed expertise in every single aspect of pediatric care,” said David H. Perlmutter, M.D., physician-in-chief and scientific director, Children’s Hospital, and Distinguished Professor and Vira I. Heinz Endowed Chair, Department of Pediatrics, Pitt School of Medicine. “From the research that is done to develop a specific therapy, to the multidisciplinary team that puts the care program together and helps the family to execute it, our work gives hope for families.”

According to the National Institutes of Health (NIH), a rare or “orphan” disease is one that affects fewer than 200,000 individuals in the United States. Today, there are nearly 7,000 different rare diseases and disorders, with more being discovered every day.

Children’s treats a multitude of rare diseases, including Byler disease, combined immune deficiency syndrome, Hurler syndrome, Krabbe disease, glycogen storage disorders, maple syrup urine disease (MSUD), and many more. Internationally renowned physicians at the hospital who are experts in their fields include:

  • Maria Luisa Escolar, MD, MS, director, Program for the Study of Neurodevelopment in Rare Disorders
  • Ira Fox, MD, director, Center for Innovative Regenerative Therapies
  • Mark Lowe, MD, PhD, chief, Division of Gastroenterology, Hepatology, and Nutrition
  • George V. Mazariegos, MD, FACS, chief, Pediatric Transplantation
  • Michael Moritz, MD, clinical director, Pediatric Nephrology
  • Ken K. Nischal, MD, FRCOphth, chief, Division of Pediatric Ophthalmology, Strabismus, and Adult Motility
  • David H. Perlmutter, MD, physician-in-chief and scientific director, and chair, Pediatrics
  • Robert Squires, MD, Pediatric Hepatology Program
  • Paul Szabolcs, MD, chief, Bone Marrow Transplantation and Cellular Therapies
  • Jerry Vockley, MD, PhD, chief, Medical Genetics

In addition, the center actively collaborates with physicians and institutions engaged in researching and diagnosing rare diseases in children and supporting them and their families. One example is the ongoing collaboration with the Clinic for Special Children in Strasburg, Pa. In collaboration with the clinic, Children’s became the world’s first hospital to establish a liver transplantation protocol for patients with MSUD and now more than 50 children with MSUD have received liver transplants here. By concentrating on specific rare diseases, like MSUD, the new center is able to bring together its experts and form necessary collaborations to focus on the advancement of innovative therapies.

For more information on the Center for Rare Disease Therapy, visit www.chp.edu/rarecare.

Erectile Dysfunction Drugs Could Protect Liver from Sepsis-Induced Damage, Says Pitt Team

PITTSBURGH, Jan. 29, 2015 – Drugs that are on the market to treat erectile dysfunction (ED) could have another use—they might be able to protect the liver from damage caused by sepsis, a systemic inflammatory response to infection, say researchers at the University of Pittsburgh School of Medicine. They recently published their findings in Science Signaling.

Infection can lead to the release of chemicals that cause whole-body inflammation, which can cause life-threatening damage to organs including the liver and kidneys, explained senior investigator Timothy Billiar, M.D., professor and chair of surgery, Pitt School of Medicine. Sepsis is a leading cause of death in the intensive care unit.

“Sepsis is a very challenging problem, so the possibility that we might be able to repurpose a drug that is in use and well understood is very exciting,” Dr. Billiar said.

Sepsis triggers production of a protein called tumor necrosis factor, or TNF, which helps fight infection but is harmful at sustained high levels. The researchers found in a mouse model of sepsis that sildenafil, more commonly known as Viagra, induced the liver to produce greater amounts of a protein called cyclic GMP, which in turn led cells to shed surface proteins called TNF receptor, reducing TNF signaling in the cells and preventing  liver damage. Experiments with human liver cells also showed the protective effects of the drug.

“Our study suggests that increasing the bioavailability of cyclic GMP might be beneficial in ameliorating the inflammation associated with sepsis,” Dr. Billiar said. “Sildenafil and other ED drugs might be a good approach to try early in the course of the illness to forestall organ damage.”

The research team plans to verify their findings in a large animal model of sepsis.

Other investigators include lead author Meihong Deng, Ph.D., Patricia A. Loughran, Ph.D., Liyong Zhang, Ph.D., and Melanie J. Scott, M.D., Ph.D., all of the University of Pittsburgh. The project was funded by National Institutes of Health grants GM044100 and GM050441.

Dementia Expert Invited to Attend Young Leaders in Dementia Event at British Embassy

PITTSBURGH, Jan. 26, 2015 – Eric McDade, DO, assistant professor in the University of Pittsburgh Department of Neurology, has been invited to attend the U.S. Young Leaders Discussion Series for Innovative Ideas to Address Dementia on Feb. 9, 2015 at the British Embassy in Washington, D.C. The UK Science and Innovation Network organized the event as part of a series of young leaders events in parallel with the Global Action Against Dementia (GAAD) Legacy Events to raise awareness of the UK G8 Dementia Summit and create a network of young leaders who can contribute to the work of the UK-initiated World Dementia Council (WDC).

The discussion series will give young leaders the opportunity to develop innovative ideas to support the ongoing work of the WDC, and to create a sustainable global network, which will continue to address the challenges presented by dementia.

The goals of the events are to:

  • Create a virtual global network of future young leaders in dementia
  • Establish a ‘Young Innovators Declaration’ to address issues in dementia for the future
  • Contribute to GAAD and WDC strategies

Dr. McDade’s clinical focus is on dementia with interests in frontotemporal dementia, Alzheimer dementia, Lewy body dementia, and young-age onset dementias, as well as familial dementia syndromes. He also evaluates patients at the University of Pittsburgh Alzheimer’s Disease Research Center (ADRC), and contributes to clinical trials in Alzheimer’s disease.

Through his interest in familial dementia syndromes, Dr. McDade serves as the University of Pittsburgh’s principal investigator for the Dominantly Inherited Alzheimer Network (DIAN), an international, multi-site study of autosomal dominant Alzheimer’s.

For more information about the discussion series, please visit the UK Science & Innovation Network webpage.

Pitt Effort Seeks to Combat ‘Sitting Disease,’ Diabetes with $3M NIH Grant

PITTSBURGH, Jan. 26, 2015 University of Pittsburgh Graduate School of Public Health researchers are flipping conventional thought on its head regarding how to improve the health of sedentary people at risk for diabetes and heart disease in a new study designed to combat a condition popularly called “sitting disease.”

Armed with a $3 million grant from the National Institutes of Health (NIH), physical activity epidemiologist Andrea Kriska, Ph.D., and her team will investigate whether they can improve the health of sedentary, overweight people with a program initially focusing on decreasing the amount of time they spend sitting – rather than starting with an emphasis on increasing the amount of time they spend exercising. This current study will test the concept that sitting less may be as important as participating in planned bouts of moderate intensity physical activity in sedentary people.

“To maintain a healthy lifestyle,  national recommendations are that you get a minimum of about two-and-a-half hours of moderate to vigorous physical activity every week – but we know that there are a lot of people who do little, if any, physical activity on a regular basis,” said Dr. Kriska, professor in Pitt Public Health’s Department of Epidemiology. “For those people, getting them to exercise might not be as initially effective as working at the other end of the activity spectrum by trying to decrease the amount of time they spend sitting.”

The grant will be used to create a new, alternate version of the Group Lifestyle Balance™ (GLB) program, a lifestyle program designed for overweight and inactive individuals who want to improve their health. The GLB program was modified for use in public health from the highly successful lifestyle intervention utilized in the U.S. Diabetes Prevention Program clinical research trial, which demonstrated for the first time – in sites across the U.S. – that people at risk for diabetes who lost weight and increased their physical activity levels sharply reduced their risk for diabetes and heart disease, outperforming people who took a diabetes drug instead. Developed here in Pittsburgh by faculty from Pitt Public Health’s Diabetes Prevention Support Center, the GLB has been shown to be effective in a variety of diverse community settings, ranging from the worksite and the military to community senior centers and primary care facilities.

The GLB program involves 22 sessions delivered over the course of one year that focus on healthy lifestyle changes, including encouraging people to slowly and safely increase their levels of physical activity. The program introduces the idea of reducing sedentary behavior toward the end of the sessions, with the major emphasis on increasing physical activity levels throughout the program.

The new grant will put the concept of sitting less right up front as the primary movement goal.

“So at the beginning, participants are not going to start tracking how much walking and biking they do. Instead, they’re going to think about how much time they spend sitting – and then start decreasing that time,” said co-investigator M. Kaye Kramer, Dr.P.H., assistant professor in Pitt Public Health’s Department of Epidemiology and director of the school’s Diabetes Prevention Support Center.

The program will seek to enroll more than 300 people age 50 and older in the Pittsburgh region. Participants will be screened to ensure that they are at risk for diabetes or metabolic syndrome in order to test the program on those most likely to benefit from it. The research team will track participants’ weight, waist circumference, blood glucose and fat levels, blood pressure, physical function, quality of life and, of course, changes in sedentary behavior and physical activity.

“We believe that we’re going to see an increase in overall movement by encouraging people to sit less,” said Dr. Kriska. “And that will lead to a whole host of health improvements, from weight loss to decreasing risk factors for diabetes and heart disease.”

Additional investigators on this project are Bonny Rockette-Wagner, Ph.D., Vincent Arena, Ph.D., Elizabeth Venditti, Ph.D., Rachel Miller, M.S., Tom Songer, Ph.D., and Jennifer Brach, Ph.D., P.T., all of Pitt.

People interested in learning more about the new study can visit Pitt’s Diabetes Prevention Support Center at www.diabetesprevention.pitt.edu.

Pitt Researcher Receives Innovation Award for Parkinson’s Research

PITTSBURGH, Jan. 23, 2015 – Laurie Sanders, Ph.D., assistant professor of neurology in the Pittsburgh Institute of Neurodegenerative Diseases, University of Pittsburgh Department of Neurology, will receive the William N. & Bernice E. Bumpus Foundation Innovation Award. The Innovation Award is designed to provide support for the next generation of exceptionally creative thinkers with “high risk/high reward” ideas that have the potential to significantly impact the understanding of the cause and prevention of Parkinson’s disease.

The $300,000 award will enable Dr. Sanders to further investigate the underlying mechanisms of neurodegeneration in Parkinson’s disease. There is strong evidence that oxidative damage to proteins and lipids are a contributing factor to the development of Parkinson’s, but very little is known about unrepaired mtDNA damage, which has been shown to lead to cell death. Dr. Sanders’ research will focus on the events that lead to mtDNA damage and could lead to crucial advances in the understanding of Parkinson’s disease and experimental therapeutics.

UPMC Approved to Perform Kidney Transplants at UPMC Hamot

ERIE, Pa., Jan. 22, 2015 – The private organization that manages the nation’s organ sharing network has given approval for UPMC surgeons to start performing kidney transplants at UPMC Hamot. The decision by the United Network for Organ Sharing (UNOS) means kidney recipients in northwestern Pennsylvania will have access to the same world-class care offered at UPMC hospitals in Pittsburgh, where organ transplantation was pioneered and perfected.

UPMC officials expect to begin performing  kidney transplant surgeries, with organs from both living and deceased donors, at Hamot starting this summer. It will mark the first time that UPMC has performed transplant surgeries outside of Pittsburgh.

“This is a really exciting time for the UPMC transplant program. Over the last several years, we’ve expanded our clinics across western Pennsylvania and are seeing more patients for clinic visits where they live, instead of having them travel to Pittsburgh,” said Abhinav Humar, M.D., UPMC’s chief of transplantation. “Now we have our first opportunity to perform transplant surgeries outside of Pittsburgh, and hopefully offer this lifesaving procedure to many more people living with kidney disease.”

Officials estimate that about 250 patients who are currently being evaluated for transplants, are on the waiting list, or are post-transplant will have their care transferred from Pittsburgh to Hamot.  Over the next few months, officials at UPMC Hamot plan to spread the word about the new program through community outreach and town hall meetings. Dates for the meetings are still being determined.

“UPMC has led the way in organ transplantation, from performing first-of-its kind procedures to developing drug regimens that made it possible for transplant survivors to thrive. Now patients can stay here in our community to get the benefit of these amazing innovations,” said David P. Gibbons, M.H.A., R.N., UPMC Hamot’s chief operating officer.

The transplant team at Hamot is currently being assembled and will consist of individuals based at Hamot as well as individuals from the transplant program at Pittsburgh, allowing for a close partnership with the University of Pittsburgh’s Thomas E. Starzl Transplantation Institute. The institute’s namesake, Dr. Starzl, is considered by many to be the father of transplantation.

Since 1981, UPMC has performed more than 17,000 organ transplants, and has developed some of the most extensive clinical expertise in the field, giving hope to patients across the country and around the world.

New Machine-Perfusion Organ Preservation System Keeps Livers Healthier for Transplant

PITTSBURGH, Jan. 22, 2015 – A new preservation system that pumps cooled, oxygen-rich fluid into donor livers not only keeps the organs in excellent condition for as long as nine hours before transplantation, but also leads to dramatically better liver function and increases survival of recipients, according to a series of animal studies by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. The system could be tested with transplant patients at UPMC later this year.

The findings, which were published online in the American Journal of Transplantation, suggest that it’s possible to use the technique of “machine perfusion” with a newly created cell-free oxygenated solution to expand the number of high-quality livers available for transplant, thereby shortening waiting times and reducing patient mortality.

Currently, 20 to 40 percent of donor livers cannot be transplanted into recipients because oxygen deprivation during storage and transport in conventional containers can make pre-existing tissue damage worse, explained senior investigator Paulo Fontes, M.D., UPMC transplant surgeon, associate professor, Starzl Transplantation Institute, Department of Surgery, Pitt School of Medicine, and a deputy director of the McGowan Institute. If the damage is too extensive, the organ cannot be safely transplanted into a patient.

“Standard practice is to use a method called cold static preservation, which uses tissue cooling to slow down metabolism with the aim of reducing the demand for oxygen and thus protecting cells from death,” Dr. Fontes explained. “In our new system, we pump a special fluid designed to deliver oxygen to the liver, creating an environment that supports normal function. The integrity of the cells and vital metabolic activity is sustained for eventual transplantation of the organ.”

The research team optimized a machine-perfusion (MP) device that was developed by Organ Assist, a company in the Netherlands, and added a fluid with a hemoglobin-oxygen carrier component to deliver high concentrations of oxygen to the tissue. The liver is immersed in chilled fluid, which is also pumped through tubes inserted into the organ’s large blood vessels to effectively oxygenate the tissue.

The team transplanted six pigs with livers that had been kept for nine hours, roughly the average time between recovery of the organ and transplantation into a recipient, in the MP system and another six with organs placed in the standard container.

They found that 100 percent of the pigs who got MP livers survived, compared to 33 percent of those who received conventionally preserved organs. The MP livers functioned better, produced more bile and had higher oxygen levels than their conventional counterparts, and analyses of multiple biomarkers including inflammatory mediators indicated that the MP livers had been better preserved.

Also, “it was immediately obvious to us that the pigs who received MP livers looked much healthier and easily moved around their pens just hours after they woke up from the surgery,” Dr. Fontes said. “They didn’t look as ill as the animals treated with standard cold preservation. It was amazing.”

The data from the studies have been shared with federal regulators, he added, with the aim of launching a clinical trial to test the system at UPMC this year.

“This system has great potential to enhance our current standards for organ preservation, which should translate into more patients getting a life-saving procedure with potentially better outcomes,” Dr. Fontes said. “Not only that, we have hopes of a faster recovery because the liver could be less likely to become injured due to a lack of oxygen.”

Co-investigators include Roberto Lopez, M.D., Yoram Vodovotz, Ph.D., Marta Minervini, Ph.D., Victor Scott, M.D., Kyle Soltys, M,D., Sruti Shiva, Ph.D., Shirish Paranjpe, Ph.D., David Sadowsky, Derek Barclay, Ruben Zamora, Ph.D., Donna Stolz, Ph.D., Anthony Demetris, M.D., George Michalopoulos, M.D., Ph.D., and James Wallis Marsh, M.D., all of the University of Pittsburgh; and Arjan van der Plaats, Ph.D., of Organ Assist, Groningen, Netherlands.

The study was funded by a charitable gift from Mr. and Mrs. Garcia de Souza, as well as grant DK072146 from the National Institutes of Health.

UPMC Sports Medicine Concussion Program Releases Research Review

PITTSBURGH, Jan. 21, 2015 – The UPMC Sports Medicine Concussion Program has released its 2014 summary of concussion research trends, new research initiatives, publications, and ongoing collaborations from their Research Laboratory.

The UPMC Sports Medicine Concussion Program is under the leadership of director Michael Collins, PhD, associate professor of orthopaedic surgery in the Division of Sports Medicine, and assistant research director Anthony Kontos, PhD, associate professor of orthopaedic surgery in the Division of Sports Medicine.

Research initiatives of the Concussion Program continue to center on advances in empirically based assessment, neuroimaging, targeted treatments, and the effects of concussion in youth sport populations. Much of this research continues to focus on advancing the current clinical standard of care for assessing and treating this injury.

Key research and collaborations featured in the report include,

  • “Targeted Evaluation, Action, and Monitoring for TBI (TEAM-TBI),” a $4.4 million project funded by the United States Department of Defense that focuses on providing veterans and active duty military personnel with a comprehensive assessment and targeted clinical interventions for mild traumatic brain injuries (mTBI).
  • The NFL-GE Head Health Initiative grant to identify concussion and track recovery in athletes using high definition fiber tracking (HDFT) and other clinical measures.
  • Select published papers from UPMC and University of Pittsburgh faculty that were featured in peer-reviewed journals such as the American Journal of Sports Medicine, Pediatrics, and Brain Imaging and Behavior.
  • An ongoing, first-of-its-kind initiative funded by the National Collegiate Athletic Association (NCAA) and the Department of Defense Grand Alliance, and in partnership with Indiana University, the Medical College of Wisconsin, and the University of Michigan, to collect data on NCAA athletes from all sports and military personnel to gain understanding into the multidimensional predictors and outcomes associated with sports-related concussion.
  • President Barack Obama’s selection of Dr. Collins and Dr. Kontos to be among the few chosen clinical and research experts on concussion invited to attend the Healthy Kids and Safe Sports Concussion Summit at the White House where $86 million in funding from various stakeholders was announced.

For more information, please read the full Research Review.

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